The kidneys play an important role in regulating hepatic urea and extrarenal glutamine formation. During metabolic acidosis, partition of precursor nitrogen favors glutamine synthesis; urea formation decreases. Removing the kidneys results in a reversal of this partitioning: extrarenal glutamine synthesis falls while urea formation rises. Three critical questions are answered by this proposal; (1) how are urea and glutamine synthesis affected by acidosis; (2) where does acidosis increase glutamine synthesis and; (3) what signal is emitted by the kidneys to govern urea and glutamine formation. To answer: (1) glutamine and urea turnovers are measured using N15 - NH3 and analyzing glutamine and urea pools in control and acidotic rats; (2) glutamine A-V differences are measured across suspected important organ vasculature beds as well as determining tissue N15 - glutamine specific activity and; (3) bilateral ureteral ligation is compared to differentiate excretory from renal metabolic function in regulating (1) and (2), and renal vein contents are analyzed for a signal (renal NH3 production) which could act to inhibit urea and stimulate extrarenal glutamine synthesis. These results will elucidate the mechanism by which the kidneys govern urea and glutamine formation to harmonize extrarenal nitrogen metabolism with enhanced renal glutamine utilization in metabolic acidosis.